We study the forces that govern the transport of DNA and other molecules through nanopores. Our experimental efforts combine optical tweezers, fluorescence sensing and electrophysiology (ionic current sensing). Our aim is to gain novel insights and translate our findings into nanopore systems with enhanced sensing capabilities. We want to enhance the specificity, sensitivity and durability of nanopore sensors. Our nanopore systems are made out of glass nanopores, nanopores in thin silicon-based membranes, and in sheets of graphene and hBN.
Casey, Filip, Jinbo, Kaikai, Mohammed, Sarah
Sandip Ghosal (Northwestern University), Murugappan Muthukumar (University of Massachusetts, Amherst)
K. Chen, I. Jou, N. Ermann, M. Muthukumar, U. F. Keyser, and N. A. W. Bell.Nature Physics, 17(9):1043-1049, 2021. [ DOI | http ]
N. A. W. Bell and U. F. Keyser. Nature Nanotechnology, 11:645-651, 2016.[ DOI | .html ]
U. F. Keyser. J. R. Soc. Interface, 8:1369-1378, 2011. [ DOI | http ]
Passive membrane transport is ubiquitous in living organism. One class of special interest are small organic compounds like indole. In many respects indole behaves like the signalling component of a quorum sensing system. Indole synthesised within the producer bacterium is exported into the surroundings where its accumulation is detected by sensitive cells. By direct observation of indole import into individual liposomes we have shown that indole can cross a lipid membrane without the aid of a proteinaceous transporter and provide a simple explanation for the ability of indole to signal between biological Kingdoms.
Our microfluidic technique enables quantification of drug transport through lipid membranes. Since passive transport accounts for over 80% of drug uptake in cells it has special relevance for the understanding of antibiotic resistance. Giant unilamellar vesicles (GUVs) are used as model membranes; the lipid composition of these membranes is fully controlled. Our optofluidic assay directly measures the Permeability Coefficient of a drug crossing lipid membranes. We are able to screen the permeability properties of various autofluorescent drugs in a lipid specific manner, without needing to resort to octanol partition coefficient measurements. Furthermore, we can study the effect of membrane proteins on drug transport. We are now using our system to quantify drug transport in highly controlled environments with special emphasis on clarifying the role of outer membrane channels in antibiotics resistance.
Jehangir, Marcus, Ran
Tuomas Knowles (Chemistry), Max Ryadnov (NPL), Stefano Pagliara (Exeter), Mathias Winterhalter (JU Bremen), David Summers (Genetics, Cambridge), Fiona Gribble and Frank Reimann (Institute for Medical Research, Cambridge)
M. Schaich, et al. Mol. Pharmaceutics, 16(6):2494-2501, 2019. [ DOI | http ]
K. Al Nahas, et al.
J. Cama, et al. JACS, 137(43):13836-13843, 2015. [ DOI | http ]